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Pyrazolopyrimidine-type compound, and preparation method and application thereof

A pyrazolopyrimidine and azolopyrimidine technology, which is applied in the field of pyrazolopyrimidine compounds and their preparation, can solve the problems of poor therapeutic effect and uniform drug resistance of targeted therapy drugs, and achieve low cost and high synthesis efficiency. The effect of short route and simple operation process

Inactive Publication Date: 2018-11-02
GUANGZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Poor clinical efficacy of some drugs and drug resistance of approved targeted therapy drugs are related to

Method used

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  • Pyrazolopyrimidine-type compound, and preparation method and application thereof
  • Pyrazolopyrimidine-type compound, and preparation method and application thereof
  • Pyrazolopyrimidine-type compound, and preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0057] An embodiment of the preparation method of pyrazolopyrimidine compounds of the present invention, the compound name is 7-[2-fluoro-4-(3,5,6-trimethylpyrazinecarboxamido)phenoxy] -5-methylpyrazolo[1,5-a]pyrimidine, the R group is 3,5,6-trimethylpyrazine, and the preparation method comprises the following steps:

[0058] (1) Synthesis of intermediate 5-methyl-7-hydroxy-pyrazolo[1,5-a]pyrimidine

[0059] Weigh 4.860g (58.000mmol) of 3-aminopyrazole and 7.541g (58.000mmol) of ethyl acetoacetate into a round bottom flask, add 20mL of glacial acetic acid as the reaction solvent, heat and stir, and react at 120°C for 1.5h. TLC detection; after the reaction is finished, cool, filter with suction, and wash the upper precipitate with absolute ethanol to obtain 6.103 g of a white solid, which is the intermediate 5-methyl-7-hydroxyl-pyrazolo[1,5-a ] pyrimidine ( 1 H NMR and 13 C NMR spectrum as figure 1 Shown), productive rate 70%;

[0060] 1 H NMR (400MHz, DMSO-d 6 )δ12.28(...

Embodiment 2

[0080] An embodiment of the preparation method of pyrazolopyrimidine compounds of the present invention, the compound name is 7-[2-fluoro-4-(pyrazinecarboxamido)phenoxy]-5-methylpyrazolo[ 1,5-a] pyrimidine, R base is 2-pyrazinyl, and the preparation method comprises the following steps:

[0081] (1) Synthesis of intermediate 5-methyl-7-hydroxy-pyrazolo[1,5-a]pyrimidine

[0082] Weigh 69.600mmol of 3-aminopyrazole and 58.000mmol of ethyl acetoacetate into a round bottom flask, add 20mL of glacial acetic acid as a reaction solvent, heat and stir, react at 100°C for 2.5h, and detect by TLC; after the reaction, cool , filtered with suction, and washed the upper precipitate with absolute ethanol to obtain 6.103 g of a white solid, which is the intermediate 5-methyl-7-hydroxy-pyrazolo[1,5-a]pyrimidine, with a yield of 70%;

[0083] (2) Synthesis of intermediate 5-methyl-7-chloro-pyrazolo[1,5-a]pyrimidine

[0084] Weigh 2.500g (16.800mmol) of 5-methyl-7-hydroxy-pyrazolo[1,5-a]pyrim...

Embodiment 3

[0094] An embodiment of the preparation method of pyrazolopyrimidine compounds of the present invention, the compound name is 7-[2-fluoro-4-(5-pyrimidinecarboxamido)phenoxy]-5-methylpyrazolo [1,5-a]pyrimidine, the R group is 5-pyrimidinyl, and the preparation method comprises the following steps:

[0095] (1) Synthesis of intermediate 5-methyl-7-hydroxy-pyrazolo[1,5-a]pyrimidine

[0096] Weigh 63.800mmol of 3-aminopyrazole and 58.000mmol of ethyl acetoacetate into a round bottom flask, add 20mL of glacial acetic acid as a reaction solvent, heat and stir, react at 140°C for 1.8h, and detect by TLC; after the reaction, cool , filtered with suction, and washed the upper precipitate with absolute ethanol to obtain 6.103 g of a white solid, which is the intermediate 5-methyl-7-hydroxy-pyrazolo[1,5-a]pyrimidine, with a yield of 70%;

[0097] (2) Synthesis of intermediate 5-methyl-7-chloro-pyrazolo[1,5-a]pyrimidine

[0098] Weigh 2.500g (16.800mmol) of 5-methyl-7-hydroxy-pyrazolo[1...

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Abstract

The invention discloses a pyrazolopyrimidine-type compound. The structural general formula of the pyrazolopyrimidine-type compound is shown as formula (I). The invention further discloses a preparation method of the pyrazolopyrimidine-type compound and application of the pyrazolopyrimidine-type compound in preparation of antitumor drugs. The provided pyrazolopyrimidine-type compound can effectively inhibit multipletumor cells, including human breast cancer cells, human lung cancer cells, human hepatoma carcinoma cells, human neuroblastoma cells and the like, has high antitumor activity and canbe applied to preparation of the antitumor drugs.

Description

technical field [0001] The invention belongs to the technical field of chemical medicines, and in particular relates to a pyrazolopyrimidine compound and its preparation method and application. Background technique [0002] c-Met is a receptor for hepatocyte growth factor (HGF) and a member of the heterodimeric receptor tyrosine kinase (RTKs) subfamily. When HGF binds to the receptor c-Met, cell signals are extensively transduced, including participating in cell proliferation, movement, migration and invasion. Importantly, aberrant HGF / c-Met signaling is a driver of multiple malignancies, promoting tumor growth, invasion, dissemination, and angiogenesis. Poor clinical efficacy of some drugs and drug resistance of approved targeted therapy drugs are related to [0003] Abnormal HGF / c-Met signaling. Therefore, c-Met kinase is expected to be a target for tumor drug development. Contents of the invention [0004] Based on this, the purpose of the present invention is to ov...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D487/04A61K31/513A61P35/00
CPCA61P35/00C07D487/04
Inventor 张超梁昕彤谢国权罗国林吴文浩喻丽红
Owner GUANGZHOU MEDICAL UNIV
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